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Zero and 1st Order Kinetics
For almost all drugs, the metabolism rate in any given pathway has an upper limit (capacity limitation). However, at therapeutic concentrations of most drugs, usually only a small fraction of the metabolizing enzyme's sites are occupied, and the metabolism rate increases with drug concentration. In such cases, called 1st-order elimination (or kinetics), the metabolism rate of the drug is a constant fraction of the drug remaining in the body (rather than a constant amount of drug per hour); ie, the drug has a specific half-life. For example, if 500 mg is present in the body at time zero, after metabolism, 250 mg may be present at 1 h and 125 mg at 2 h (illustrating a half-life of 1 h). However, when most of the enzyme sites are occupied, metabolism occurs at its maximal rate and does not change in proportion to drug concentration; ie, a fixed amount of drug is metabolized per unit time (zero-orderkinetics). In this case, if 500 mg is present in the body at time zero, after metabolism, 450 mg may be present at 1 h and 400 mg at 2 h (illustrating a maximal clearance of 50 mg/h and no specific half-life). As drug concentration increases, metabolism shifts from 1st-order to zero-order kinetics.
Welcome to the Drug Action and Adverse Reactions Development Page=
Zero and 1st Order Kinetics
For almost all drugs, the metabolism rate in any given pathway has an upper limit (capacity limitation). However, at therapeutic concentrations of most drugs, usually only a small fraction of the metabolizing enzyme's sites are occupied, and the metabolism rate increases with drug concentration. In such cases, called 1st-order elimination (or kinetics), the metabolism rate of the drug is a constant fraction of the drug remaining in the body (rather than a constant amount of drug per hour); ie, the drug has a specific half-life. For example, if 500 mg is present in the body at time zero, after metabolism, 250 mg may be present at 1 h and 125 mg at 2 h (illustrating a half-life of 1 h). However, when most of the enzyme sites are occupied, metabolism occurs at its maximal rate and does not change in proportion to drug concentration; ie, a fixed amount of drug is metabolized per unit time (zero-order kinetics). In this case, if 500 mg is present in the body at time zero, after metabolism, 450 mg may be present at 1 h and 400 mg at 2 h (illustrating a maximal clearance of 50 mg/h and no specific half-life). As drug concentration increases, metabolism shifts from 1st-order to zero-order kinetics.